The advance from endoscopic mucosal resection (EMR) to endoscopic submucosal dissection (ESD) has enabled
We have previously reported the use of endoscopic ultrasonography (EUS) to identify vasculature in the submucosa beneath the lesion and thereby predict the risk of intraoperative bleeding during ESD [
This study was commenced after obtaining approval from the Ethics Committee at Toranomon Hospital in June 2008. Inclusion criteria were (1) age ≥20 years, (2) gastric tumor treated by ESD, (3) having received EUS prior to ESD, and (4) having provided written informed consent. Patients were excluded if they (1) had multiple resectable gastric lesions, (2) had undergone any surgical procedure involving the stomach or esophagus, (3) had a lesion that extended to the esophagogastric junction or pyloric ring, (4) had a ulcer scar that made it difficult to identify the layer structure of the gastric wall by EUS, (5) had serious liver/kidney dysfunction or hematological disorder, (6) were receiving antiplatelet or anticoagulation therapy, or (7) were considered inappropriate for participation in this study by the attending physician.
A total of 110 patients were enrolled in this study between August 2008 and June 2010. Of them, 89 were included for analysis, and the following were excluded: 12 who were found after entry to be receiving antithrombotic therapy, 4 in whom multiple lesions were resected during ESD, 3 who were followed up without treatment after EUS, 1 who underwent surgery after EUS, and 1 who underwent stepwise biopsy, but not EUS, due to an irregularly bordered lesion (Figure
Flow of patients through this study.
EUS was performed to determine the invasion depth of the lesion prior to ESD. During EUS, a deaerated water-filling method was used for the observation using a 20 MHz miniature probe (Olympus Optical, Tokyo, Japan). The gastric wall was visualized as consisting of 5 layers. A hyperechoic line observed in the third layer was identified as the submucosa and a hypoechoic line observed in the fourth layer was identified as the muscularis propria. Lesions were classified into the following two groups according to the vascular structure identified by EUS in the third layer: group P, lesions with almost no hypoechoic areas likely to represent blood vessels or with ≤4 vessels of 50
Endoscopic image of a patient in group P showing a flat elevated lesion on the posterior wall of the middle gastric body (yellow arrow).
EUS image of the lesion of Figure
Post-ESD image of the lesion of Figure
Endoscopic image of a patient in group R showing a depressed lesion on the posterior wall of the lower gastric body (yellow arrow).
EUS image of the lesion of Figure
Post-ESD image of the lesion of Figure
ESD was performed by skilled endoscopists who had experienced more than 100 cases of gastric ESD. Endoscopists under training were also allowed to perform the procedure under the guidance and supervision of the skilled endoscopists, who was blinded to EUS findings when performing ESD. ESD was performed using a GIF Q260J or 2TQ 260 M endoscope (Olympus Optical, Tokyo, Japan), a Flex or Dual knife (Olympus Optical, Tokyo, Japan) in all cases, plus a Hook knife (Olympus Optical, Tokyo, Japan) in some cases at the discretion of the operator, and an ICC 200 or VIO 300D high-frequency apparatus (ERBE, Tübingen, Germany).
Some marks were placed around the lesion, Glyceol (Chugai Pharmaceutical, Tokyo, Japan) was injected locally, and an incision was made around the lesion. With the submucosa identified under direct view, the lesion was separated from the submucosa to obtain
This study was performed as a prospective observation study. The primary endpoint was the decrease in Hb after ESD compared with before ESD. The secondary endpoints were (1) total procedure time, (2) incidence of injury or perforation of the muscle layer during ESD, (3) incidence of clip use during ESD, (4) incidence of postoperative fever of ≥38°C, (5) incidence of postoperative bleeding, and (6) percentage of patients who resumed eating on the day after ESD. The total procedure time was defined as the interval from the start of marking to completion of resection. Perforation was defined as the presence of free air or mediastinal emphysema on postoperative X-ray. Muscle layer injury was defined as exposure and partial tearing of the muscularis propria, without perforation, during ESD.
Pathological examination of the resected specimen was performed using parallel 2 mm thick sections stained with hematoxylin and eosin in accordance with the Japanese classification of gastric carcinoma [
Data were analyzed using the unpaired
Clinical characteristics of two groups.
Group P | Group R |
|
|
---|---|---|---|
Number of patients | 50 | 39 | |
Gender (male/female) | 37/13 | 33/6 | 0.23 |
Mean age (years ± SD†) |
|
|
0.90 |
Location (U/M/L) | 3/10/37 | 16/12/11 | <0.001 |
Gross type (elevated/others) | 15/35 | 13/26 | 0.74 |
Mean maximum diameter of tumor (mm ± SD) |
|
|
0.18 |
Mean maximum diameter of specimen (mm ± SD) |
|
|
0.06 |
Tumor depth (mucosal cancer/submucosal cancer) | 47/3 | 28/11 | 0.004 |
The mean decrease in Hb, the primary endpoint, was 0.27 g/dL in group P and 0.35 g/dL in group R, with no significant difference between groups. Perforation occurred in only 1 (1.1%) patient in group R, and therefore no significant difference was found in the incidence of perforation between groups. The total procedure time was significantly longer in group R (105.4 min) compared with group P (65.5 min) (
The incidence of muscle layer injury and that of clip use were not significantly different depending on the location of lesions, but tended to be higher in regions U/M and L in group R, respectively. The procedure time for lesions in region U/M was longer in group R, but not significantly (Table
Overall results of this study.
Group P |
Group R |
|
|
---|---|---|---|
Mean decrease in Hb† (g/dL ± SD‡) |
|
|
0.56 |
Mean procedure time (min ± SD) |
|
|
<0.001 |
Incidence of perforation, % ( |
0.0 (0) | 2.6 (1) | 0.25 |
Incidence of clip use, % ( |
20.0 (10) | 48.7 (19) | 0.004 |
Incidence of muscle injury, % ( |
8.0 (4) | 25.6 (10) | 0.023 |
Incidence of postoperative fever, % ( |
4.0 (2) | 7.7 (3) | 0.45 |
Incidence of postoperative bleeding, % ( |
4.0 (2) | 7.7 (3) | 0.45 |
Percentage of patients who resumed eating on the day after ESD, % ( |
84.0 (42) | 82.1 (32) | 0.81 |
Results for lesions in region U/M.
Group P ( |
Group R |
|
|
---|---|---|---|
Mean decrease in Hb† (g/dL ± SD‡) |
|
|
0.55 |
Mean procedure time (min ± SD) |
|
|
0.28 |
Incidence of perforation, % ( |
0.0 (0) | 3.6 (1) | 0.49 |
Incidence of clip use, % ( |
38.5 (5) | 57.1 (16) | 0.27 |
Incidence of muscle injury, % ( |
15.4 (2) | 28.6 (8) | 0.36 |
Incidence of postoperative fever, % ( |
7.7 (1) | 10.7 (3) | 0.76 |
Incidence of postoperative bleeding, % ( |
0.0 (0) | 3.6 (1) | 0.49 |
Percentage of patients who resumed eating on the day after ESD, % ( |
76.9 (10) | 82.1 (23) | 0.81 |
Results for lesions in region L.
Group P ( |
Group R |
|
|
---|---|---|---|
Mean decrease in Hb† (g/dL ± SD‡) |
|
|
0.56 |
Mean procedure time (min ± SD) |
|
|
0.002 |
Incidence of perforation, % ( |
0.0 (0) | 0.0 (0) | |
Incidence of clip use, % ( |
13.5 (5) | 27.3 (3) | 0.28 |
Incidence of muscle injury, % ( |
5.4 (2) | 18.2 (2) | 0.18 |
Incidence of postoperative fever, % ( |
2.7 (1) | 0.0 (0) | 0.58 |
Incidence of postoperative bleeding, % ( |
5.4 (2) | 18.2 (2) | 0.18 |
Percentage of patients who resumed eating on the day after ESD, % ( |
100 (37) | 81.8 (9) | 0.008 |
Invasion depth is an important criterion for selecting an appropriate treatment in early gastric cancer. Thus, prior to ESD, the invasion depth of a lesion is determined by various modalities, such as EUS. However, the diagnostic accuracy of EUS is controversial; some studies clearly demonstrate the usefulness of EUS for determining invasion depth in early gastric cancer [
The results of the present study revealed that the procedure time was significantly longer and that the incidence of clip use and muscle layer injury was significantly higher in group R than in group P, whereas no significant difference was seen in the decrease in Hb after ESD, the primary endpoint. A significant intergroup difference was observed in decrease in Hb in a previous retrospective study, but not in the present study. The most likely reason for this discrepancy is the operator’s improved skill in performing ESD. In other words, in the previous study, the operator was less skillful, and bleeding was more likely to occur from vessel-rich lesions during ESD, while in the present study, improved skills in hemostasis and prophylactic hemostasis might have led to a decreased intraoperative bleeding volume. At the same time, this might have led to an increased time required for hemostatic procedures and subsequent significant increases in total procedure time and frequency of clip use. Another possible reason for the absence of significant difference in decrease in Hb after ESD is the major influence of factors other than intraoperative bleeding, such as patient physique and fluid replacement volume.
Given that ESD for lesions in region L has been associated with a lower volume of intraoperative bleeding than lesions in other regions [
Ideally, ESD safety should be assessed on the basis of bleeding volume and incidence of perforation, and bleeding volume should be based on the actual amount of bleeding. However, since it is difficult to measure the actual amount of bleeding during ESD, the decrease in Hb was used as a surrogate measure for safety. In addition, the fact that perforation occurred in only 1 patient in group R demonstrates the safety of the procedure. Thus, other parameters, such as the incidence of muscle layer injury, incidence of clip use, and the proportion of patients who resumed eating on the day after ESD were also used as surrogate measures for safety. Overall, the incidence of muscle layer injury and clip use was significantly higher in group R than in group P. These parameters tended to be higher in group R regardless of the location of lesions, suggesting that the safety of ESD can be predicted by using EUS to some extent.
When performing ESD on lesions with abundant blood vessels in the submucosa, the operator should (1) carefully identify blood vessels under clear surgical field, (2) perform prophylactic hemostasis after identifying blood vessels, and (3) try to dissect the lesion at a deep layer of the submucosa [
There are several limitations to the present study. The first is that a single examiner evaluated EUS findings; multiple examiners may improve diagnostic objectivity and reliability. Second, the variability in skill levels of operators may also significantly affect the outcome of ESD [
In conclusion, identifying blood vessels in the submucosa by EUS does not help in predicting the risk of worsening of anemia or occurrence of perforation, but may be helpful for predicting procedure time, risk of muscle layer injury, and use of clips. The preoperative use of EUS was effective for predicting the safety of ESD and procedure time and is thus considered useful for determining ESD treatment strategy.
The authors declare that they have no conflict of interests in this research.